TNFRSF17 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | TNFRSF17, BCM, BCMA, CD269, TNFRSF13A, tumor necrosis factor receptor superfamily member 17, TNF receptor superfamily member 17 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 109545; MGI: 1343050; HomoloGene: 920; GeneCards: TNFRSF17; OMA:TNFRSF17 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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BCMA TALL-1 binding domain | |||||||||
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Identifiers | |||||||||
Symbol | BCMA-Tall_bind | ||||||||
Pfam | PF09257 | ||||||||
InterPro | IPR015337 | ||||||||
SCOP2 | 1oqd / SCOPe / SUPFAM | ||||||||
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B-cell maturation antigen (BCMAorBCM), also known as tumor necrosis factor receptor superfamily member 17 (TNFRSF17), is a protein that in humans is encoded by the TNFRSF17 gene.
TNFRSF17 is a cell surface receptor of the TNF receptor superfamily which recognizes B-cell activating factor (BAFF).[5][6][7]
Serum B-cell maturation antigen (sBCMA) is the cleaved form of BCMA, found at low levels in the serum of normal patients and generally elevated in patients with multiple myeloma (MM).[8]
The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is preferentially expressed in mature B lymphocytes, and may be important for B cell development and autoimmune response. This receptor has been shown to specifically bind to the tumor necrosis factor (ligand) superfamily, member 13b (TNFSF13B/TALL-1/BAFF), and to lead to NF-kappaB and MAPK8/JNK activation. This receptor also binds to various TRAF family members, and thus may transduce signals for cell survival and proliferation.[7]
TNFRSF17 has been shown to interact with the B-cell activating factor TNFSF13B.[9][10] A conserved domain at the N-terminus, BCMA TALL-1 binding domain, is required for binding to the TNFSF13B.[9]
TNFRSF17 is implicated in leukemia, lymphomas, and multiple myeloma[11] (see the "Mitelman Database" [12] and the Atlas of Genetics and Cytogenetics in Oncology and Haematology,[13]).
Anantibody-drug conjugate Belantamab mafodotin (GSK2857916) has evaluated in patients with relapsed/refractory multiple myeloma.[14] Belantamab mafodotin was approved in the United States in August 2020 for the treatment of patients with relapsed or refractory multiple myeloma who have received at least four prior therapies.[15]
Chimeric antigen receptor (CAR) T cells have emerged as an important therapy for multiple myeloma after first reports in preclinical and phase I clinical studies.[16] [17] A Phase 1b/2 study of JNJ-4528, a CAR-T cell therapy directed against BCMA in myeloma patients refractory to a proteasome inhibitor or immunomodulatory drug, and who had received an anti-CD38 antibody has been completed.[18]
ALLO-715 is a CAR-T therapy by Allogene Therapeutics that targets B-cell maturation antigen (BCMA).[19] As of June 2021[update], it is undergoing clinical trials for the treatment of multiple myeloma.[20] On 21 April 2021, the FDA granted Regenerative Medicine Advanced Therapy status to ALLO-715.[21] ALLO-715 is being investigated at Memorial Sloan Kettering Cancer Center and the Mayo Clinic[22] as part of the UNIVERSAL trial for multiple myeloma, on its own and in conjunction with the selective gamma secretase inhibitor nirogacestat.[20][23]
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
PDB gallery
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1oqd: Crystal structure of sTALL-1 and BCMA
1xu2: The crystal structure of APRIL bound to BCMA
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Chemokine receptor (GPCRs) |
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TNF receptor |
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JAK-STAT |
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Ig superfamily |
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IL 17 family |
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Enzyme-linked receptor |
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